tbuckley/cabot-search huggingface dataset:
Evolution of cancer treatment costs in the last 36 months in a self-funded health care in Brazil.
Authors: Joao Paulo Reis Neto, Juliana Martinho Busch, Stephen Stefani
Journal: Journal of Clinical Oncology (2023)

e18838 Background: In Brazil, cancer, in addition to being one of the main causes of illness and death, represents one of the highest public and private healthcare expenses. Regardless of the population profile, the direct costs of cancer pose as a real threat to the health system's sustainability. The objective of this study is to analyze the evolution of the use and costs of chemotherapy, targeted therapy, hormone therapy and immunotherapy. Methods: Retrospective cohort consisted of all health plan beneficiaries diagnosed with cancer and who received pharmacological treatment in the last 36 months (September/2019 to August/2022). Based on Period 1 (P1, Sep/2019 to Aug/2020), we analyzed the evolution in the other periods (P2 and P3, Sep/2020 to Aug/2021 and Sep/2021 to Aug/2022, respectively) of the use of chemotherapy and the costs involved (per capita and per patient treated). We also analyzed the evolution of expenses with oral antineoplastic agents and their proportion in relation to other routes of administration. The most prescribed therapies were analyzed. Microsoft Excel and Qlik Sense were used for relative and absolute frequencies, means and standard deviation (95% confidence intervals, significance when p &lt; 0.05). Results: During the study period, 982 beneficiaries (683, 601 and 572, respectively in P1, P2 and P3) underwent treatment with antineoplastic agents (mean age 68 years, 50.7% women). In P1, 1.6% of the total exposed received some type of chemotherapy. In the following intervals, the percentage increased to 1.7% and 2.1%, P2 and P3, respectively. Although the cost per patient treated increased by 4.7% in 36 months, the annual expense per patient, that is, the entire portfolio of the plan and not just those diagnosed with cancer, increased by 40.5%. Should be noted that the variation that occurred in P2 in relation to P1 was 7.8%, however, in P3 compared to P2, 30.3%. The proportion of patients receiving oral antineoplastics in relation to those treated remained stable (53.6%, 54.7% and 52.3%, P1, P2 and P3, respectively). Ten active principles with the highest financial consumption and corresponding to more than half of the total expenses: nivolumab, daratumumab, bevacizumab, trastuzumab, pembrolizumab, pertuzumab, enzalutamide, atezolizumab, paclitaxel and brentuximab vedotin. Conclusions: Molecular and immunological therapies have revolutionized cancer treatment and improved patient outcomes and survival, however, new treatment options represent an additional challenge. In this study, the cost of cancer treatment has increased 40.5%, especially in the last period, which coincides with the expansion of the list of mandatory coverages and due to the resumption of procedures after COVID-19. Minimizing the financial impact of the new technologies, through responsible management focused on the patient and based on the best scientific evidence, is fundamental for maintaining the sustainability.
Multimodality, online oncology learning resources: Meeting residents where they are—A pilot to create a new oncology curriculum.
Authors: Jennifer King, Phillip Pham, Ahmed Bilal Khalid, Mohamad Sabra, Jennifer E. Schwartz
Journal: Journal of Clinical Oncology (2023)

11035 Background: The Accreditation Council for Graduate Medical Education (ACGME) requires internal medicine residents to have access to different medical subspecialties, including hematology/oncology. While inpatient rotations in hematology/oncology have been associated with a decreased interest in a career in oncology, dedicated educational sessions have been shown to improve residents’ interest in the field. In recognition of different learning styles and modalities and the need for asynchronous delivery, we aimed to build an effective curriculum for oncology learners using interactive, multimodality, online learning tools and resources. Methods: Using the Canvas online learning management system, individual learning modules covering major cancer types were created. Each learning module consisted of a pre-survey assessing the learners’ evaluation of their own knowledge and comfort with the topic, a brief audio or video file covering high-yield information about the cancer type, interactive case-based questions reviewing and reinforcing the information, and a post-survey assessing the change in the learners’ evaluation of their knowledge and comfort in clinical application of the information. The pre- and post-surveys were rated on a 5-point Likert scale. Median values and interquartile ranges are reported. A one-sided t-test was used to compare responses. Results: Two fully completed learning modules have been created. The lung cancer module included a high-yield, 10-minute voice-over PowerPoint presentation followed by interactive, case-based questions. The breast cancer module used a high-yield, 10-minute podcast with an accompanying handout for notes followed by case-based interactive questions. Seven learners have completed both pre- and post-survey responses for comparison. Two were completed by PGY1, 4 by PGY2, and 1 by a PGY3 resident. Median rating of the learners’ knowledge of the specific cancer type increased from 2- Fair (1.5) on the pre-survey to 3- Neutral (1) after completing the learning module (p = 0.001). 100% of learners agreed or strongly agreed that their knowledge increased after completing the module. All 7 residents felt more comfortable with their clinical application of the cancer topic material after completing the module, median 2(1) on pre-survey vs. 3(0.5) on post-survey; p = 0.0004. Conclusions: The creation of online, multimodality learning resources has resulted in improvements in learners’ perceived knowledge and comfort with clinical application of oncology topics. Using learning science principles, this pilot project serves as the foundation for further innovative and interactive educational resources and modules created for oncology learners.
Disparities in clinical trial enrolment at a Canadian comprehensive cancer centre: A 15-year retrospective study.
Authors: Gilla Shapiro, Rena M. Conti, Anna Santiago, Tyler Pittman, Gary Rodin, Jennifer M. Jones, Heather Cole, Katherine Zeman, Susanna Sellmann, Meredith B. Rosenthal, Amit M. Oza, Danielle Rodin
Journal: Journal of Clinical Oncology (2023)

6550 Background: Disparities in clinical trials limit the generalizability of study findings and perpetuate disparities in treatment access and outcomes, but there is a paucity of data in the Canadian context. The objective of this study was to examine disparities in cancer clinical trial enrollment at a large, comprehensive Canadian cancer center. Methods: We conducted a retrospective cohort study of clinical trial enrollment among all newly diagnosed cancer patients (N=154,880) at the Princess Margaret Cancer Centre in Toronto, Canada (2006-2021). Multivariable Bayesian hierarchical logistic regression with random effect for most responsible physician was used to examine the correlates of clinical trial enrollment, comparing the population of enrolled and non-enrolled patients. Odds ratios were adjusted for patient variables (sex, age at diagnosis, language, geography, primary care provider), and census tract-level marginalization (residential instability, material deprivation, dependency, ethnic concentration), disease variables (cancer site and disease stage at diagnosis), and provider variables (most responsible physician (MRP), and MRP’s sex, language, medical training, and department). Results: Overall, 11.2% of patients enrolled (n=17,400) in a clinical trial, with 5-, 10-, and 15-year cumulative incidences of 12%, 15%, and 18%, respectively. Small, but significant differences were observed between enrollees and the overall patient population. Lower odds of enrollment were observed in patients who were female (adjusted odds ratio [AOR], 0.82; 95% confidence interval [CI], 0.78-0.86; p&lt;.001), ≥65 years (AOR vs &lt;40, 0.61; 95% CI, 0.56-0.65; p&lt;.001), non-English language speakers (AOR vs English, 0.72; 95% CI, 0.67-0.77; p&lt;.001), lived ≥250 km away from the cancer center (AOR vs &lt;15km, 0.71; 95% CI, 0.62-0.80; p&lt;.001), or lived in areas with greater material deprivation (AOR, 0.94; 95% CI, 0.93-0.96; p&lt;.001) or higher ethnic concentration (AOR, 0.96; 95% CI, 0.94-0.98; p&lt;.001). Greater odds of enrollment were found in patients with metastatic disease (AOR, 1.19; 95% CI, 1.13-1.25; p&lt;.001) and in those with a primary care provider (AOR, 1.69; 95% CI, 1.55-1.85; p&lt;.001). Conclusions: Disparities were observed in clinical trial enrollment, despite a publicly funded health care system. While broader prospective data collection efforts are critical to better understand the influence of patient, provider and system factors on clinical trial enrollment, these findings suggest the need for targeted strategies to increase diversity in clinical trial access.
Survival outcomes of metastasectomy and primary site resection in melanoma patients with isolated brain metastasis: A SEER analysis.
Authors: Suhib Fahmawi, Abdallah Al-Ani, Issa Asfour, Sukesh Manthri
Journal: Journal of Clinical Oncology (2023)

e21541 Background: Approximately 40–50% of Stage IV melanoma patients eventually develop brain metastases which is associated with poor prognosis. Breakthroughs in targeted and immunotherapies have improved long-term survival in advanced melanoma patients. In this new era, there is a paucity of evidence for the role of metastatectomy for melanoma patients with brain metastasis. Here, we investigate the survival benefit of metastasectomy and primary site resection in melanoma patients with isolated brain metastasis. Methods: A total of 636 patients with melanoma with isolated brain metastasis at diagnosis were extracted from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2019. Patients younger than 18 years, cases with missing information including age, gender, race, unknown stage, unknown primary site resection status, unknown metastasis site, or known metastasis to the lung, liver, or bones were excluded. Cox regression analysis estimated the prognostic value of metastasectomy and primary site resection, presented by hazard ratios (HR), among melanoma patients. Survival ratios were controlled for age, race, gender, and type of melanoma. All analyses were performed on STATA v17. Results: About 49.37% of melanoma patients with isolated brain metastasis underwent metastasectomy. Of the included sample, 25% (n = 159) underwent primary site resection. Cox regression demonstrated that metastasectomy was associated with improved survival outcomes in melanoma patients with isolated brain metastasis (HR 0.51, CI 0.42 – 0.63, p &lt; 0.001). Pooled primary site resection procedures were associated with improved survival (HR 0.64, CI 0.49 – 0.83, p = 0.001) compared to not having a primary site resection. When stratified per procedure type, “wide excision or re-excision of lesions with margins &gt; 1 cm and microscopically negative margins” was associated with improved survival (HR 0.27, CI 0.133 – 0.56, p &lt; 0.001) compared to not having surgical resection, all other primary site resection procedures had no significant improvement in survival with p &gt; 0.05. Conclusions: Metastasectomy and primary site resection significantly improved survival in melanoma patients with isolated brain metastasis. Wide excision with &gt; 1cm negative margins presents itself as the most effective surgical treatment modality in terms of improving survival for these patients. Thus, it should be attempted whenever feasible.
Ripretinib therapy in treating advanced gastrointestinal stromal tumors: A single-center analysis in a real-world setting.
Authors: Zhaoming Guan, Xinhua Zhang, Yanzhe Xia, Shaoqing Huang, Chunhui Wu, Shirong Cai, Yulong He
Journal: Journal of Clinical Oncology (2023)

e23514 Background: Ripretinib has been proven effective in inhibiting various primary and secondary mutants of KIT/PDGFRA but with limited clinical data. This study is aimed to investigate the efficacy and safety of ripretinib and prognostic predictors based on the current treatment pattern in Chinese patients in a single center. Methods: This retrospective cohort study was based on the prospectively registered database of the First Affiliated Hospital, Sun Yat-sen University. Patients with confirmed recurrent and/or metastatic GIST who received ripretinib as ≥ 2nd line therapy between June 1, 2020, and January 1, 2023 were enrolled. Results: Forty patients receiving ripretinib were enrolled. The median age of the patients was 58.0 years, and the most common primary site of tumor was the small intestine (75.0%). KIT exon 11 (65.0%) was the most common primary mutation, followed by exon 9 (20.0%). Ripretinib was administered as 2 nd - and 3 rd -line therapy in 17.5% of patients, respectively; as 4 th -line therapy in 45% of patients, and as 5 th - or later-line therapy in 20% of patients. Thirty patients who received ripretinib as &gt; = 3 rd -line therapy were eligible for efficacy evaluation. There was no complete remission. Two patients (6.7%) were partial response, and 20 (66.7%) patients were disease stable for at least 8 weeks. The median follow-up time was 18.0 months. The median progression free survival (PFS) (95% confidence interval [CI]) was 5.9 (2.0, 9.7) months, and the median overall survival (OS) was 13.8 (11.5, 16.0) months. In the univariate analysis, patients with a primary mutation in KIT exon 11 (P = 0.002), better ECOG performance status (P = 0.041), and lower tumor burden, including the number (P = 0.016) and cumulative size (P＜0.001) of tumors, had longer PFS. Patients with a primary mutation in KIT exon 11 (P = 0.019), better ECOG performance status (P＜0.001), fewer tumors (P = 0.014), and a younger age (P = 0.039) had longer OS. In the multivariate analysis, the primary mutation (P = 0.004) and the number and cumulative size of tumors (P = 0.024, P = 0.015, respectively) were independent predictors of PFS. The primary mutation (P = 0.025), the number of tumors (P = 0.002), and ECOG performance status (P = 0.002) were independent factors of OS. Ripretinib was generally well tolerated, and no unexpected toxicities were observed. The most common AEs were anemia (45%), alopecia (28%), constipation (25%), and hypoalbuminemia (25%). Grade 3/4 AEs were reported in 25% of patients, and the most common ones were hand-foot syndrome (8%), anemia (5%), and increased aspartate aminotransferase (5%). Conclusions: Ripretinib was safe and effective in Chinese patients with imatinib-resistant GISTs in a real-world setting. Primary KIT exon 11 mutation, lower tumor burden and better performance status were associated with better survival benefit.
Germline mutations and the presence of clonal hematopoiesis of indeterminate potential (CHIP) in 20,963 patients with BRCA-associated cancers.
Authors: Catherine Handy Marshall, Lukasz Gondek, Elizabeth Mauer, Calvin Y. Chao, Jun Luo, Emmanuel S. Antonarakis
Journal: Journal of Clinical Oncology (2023)

10522 Background: The contribution of germline genetics on the emergence of CHIP in patients with solid tumor malignancies is not well understood. We hypothesized that those with germline (g) alterations in homologous recombination repair genes (gHRR) and BRCA-associated cancers (breast, ovarian, prostate, pancreas) would have different rates of CHIP than those without. Methods: We analyzed a large real-world Tempus multimodal database of paired germline and somatic DNA sequencing results. CHIP was calculated based on the presence of pathogenic or likely pathogenic alterations in any one of 16 CHIP-associated genes ( ASXL1, BCOR, BCORL1, CBL, CREBBP, CUX1, DNMT3A, GNB1, JAK2, PPM1D, PRPF8, SETDB1, SF3B1, SRSF2, TET2, U2AF1) with a variant allele frequency of at least 2%. Patients with g alterations in BRCA1, BRCA2, ATM, CHEK2, and PALB2 were compared to those without gHRR alterations (sporadic). Results: In breast cancer, patients with g BRCA1 (n = 104) mutations were younger (med 43 yrs) at diagnosis compared to sporadic cases (n = 6,546 med 56yrs) but had similar rates of CHIP (3% vs 5%). Those with gPALB2 (n = 42 med age 55) had the highest rate of CHIP (14%). gBRCA2 (n = 148; med age 52), gATM (n = 57 med age 52), and gCHEK2 (n = 57 med age 53) and similar rates of CHIP (3%, 4%, 7%). In ovarian cancer, patients with gBRCA1 (n = 137 med age 53) were younger at diagnosis than sporadic cases (n = 3,979 med age 63) with similar rates of CHIP (4% vs 3%). Those with gBRCA2 (n = 83 med age 61) were similar (4%) and gPALB2 (n = 11 med age 68) had the highest rate of 9%. CHIP was not detected among patients with g ATM (n = 23 med age 61) or g CHEK2 mutations (n = 9, med age 59). In prostate cancer, 4% of patients with sporadic cases had CHIP (n = 4,183 med age 66) compared to 4% in gBRCA2 (n = 109 med age 63) and 5% in gATM (n = 44 med age 66). gCHEK2 had 17% prevalence of CHIP (n = 12 med age 66) followed by gPALB2 (n = 12 med age 69). There were no CHIP mutations found among those with g BRCA1 (n = 16 med age 64). In pancreatic cancer, patients with g BRCA2 (n = 89 med age 64) and PALB2 (n = 20 med age 62) were younger at diagnosis, compared to sporadic cases (n = 5,176 med age 67) with lower rates of CHIP (1% gBRCA2, 0 PALB2, 5% sporadic). The highest proportion was in gBRCA1 patients (n = 20 med age 63) with 10%, gCHEK2 (n = 16 med age 68) with 6% and gATM (n = 60 med age 66) with 5%. Conclusions: Despite younger age at diagnosis, patients with g BRCA1 had similar or higher rates of CHIP within breast and ovarian cancer. Women with g PALB2 alterations and breast and ovarian cancer, as well as men with g CHEK2 mutations and prostate cancer, had higher rates of CHIP. These data suggest that gHRR mutations may influence the prevalence of CHIP among patients with BRCA-associated cancers and more research is needed.
Relative and functioning sleep disturbance and fatigue: Impact on patients with ovarian cancer.
Authors: Elif Andac-Jones, Abigail Newell, Elizabeth A. Szamreta, Maria Belen Gonzalo, Juliette Hoffman, Matthew Monberg
Journal: Journal of Clinical Oncology (2023)

e24102 Background: Sleep disturbance and fatigue are prevalent among ovarian cancer patients and are associated with poor mental health and Health-related quality of life (HRQoL) outcomes; while this has been well-documented, we know less about the factors that may contribute, what cancer patients perceive as contributing to their issues, and how they describe and manage these issues across their treatment trajectory. Methods: In this qualitative study, data were collected via semi-structured interviews with 20 stage III/IV ovarian cancer patients diagnosed within three years with varied treatment trajectory, race/ethnicity, and location. A screener included PROMIS Sleep Disturbance and Fatigue measures, sociodemographics, and cancer history. Transcripts were analyzed using deductive codes of sleep and fatigue and inductive codes based on emergent themes. We identify two novel concepts of patients’ sleep and fatigue experiences: relative and functioning. Relative fatigue and sleep issues capture how patients self-report relative to different points in their treatment. Functioning concept shows how patients reinterpret and self-censor the severity and impact of their sleep and fatigue by emphasizing their ability to overcome exhaustion or insomnia. Results: All twenty patients reported persistent, debilitating fatigue, difficulty falling and staying asleep through the course of their disease, which negatively impacted their HRQoL and activities of daily living. The majority of patients struggled to complete daily chores (17/20), keep up with paid work (9/10), and maintain relationships(16/20). Although patients experience fatigue across their trajectories, the majority of patients described their fatigue as more intense during chemotherapy than maintenance therapy. Patients struggled to evaluate their current fatigue and sleep without reflecting on previous treatment experiences (relative), and continuously reinterpreted their levels of fatigue and sleep based on how much of their daily functions they could complete (functioning). Patients self-censor in reporting to meet their perceived expectations of their care provider/data collector . Although fatigue and sleep disturbance significantly impaired their HRQoL, patients framed their experiences positively and minimized their struggles. Conclusions: We conclude that PROMIS measures are important in evaluating baseline sleep disturbance and fatigue in patients with ovarian cancer. However, patients’ reporting is informed by their previous treatment experiences, subject to continued reinterpretation. Therefore 1) more nuanced and repeated measures including patients’ narratives are needed to understand the complexity of patients’ experiences; and 2) Patients’ self-censorship and filtering need to be considered. Future research will test these new concepts with a 200 patient survey.
Development and validation of a prediction model for the recurrence of stage 1 EGFR mutation positive NSCLC in patients using machine learning with WES-based gene sets.
Authors: Akiko Tateishi, Hidehito Horinouchi, Ken Takasawa, Nobuji Kouno, Takaaki Mizuno, Yu Okubo, Yukihiro Yoshida, Shun-ichi Watanabe, Mototaka Miyake, Masahiko Kusumoto, Koji Inaba, Hiroshi Igaki, Yasushi Yatabe, Masami Mukai, Katsuya Tanaka, Naoki Mihara, Kouya Shiraishi, Takashi Kohno, Yuichiro Ohe, Ryuji Hamamoto
Journal: Journal of Clinical Oncology (2023)

8563 Background: Predicting the risk of postoperative recurrence is becoming increasingly important in EGFR mutation positive ( EGFR-m) non-small cell lung cancer (NSCLC). Only a few reports conducted whole exome sequencing (WES) for genomic profiling in large scale EGFR-m NSCLC cases. Methods: We conducted WES and analyzed the clinical course of patients (pts) with NSCLC who underwent surgery between 1985 and 2019 in the PRISM project of our institute. We evaluated the EGFR-m patients’ characteristics, recurrence-free survival (RFS), and developed a prediction model using machine learning, Overlapping Group LASSO to predict whether the EGFR-m patients will recur within 5 years or not as "high-risk" and "low-risk". To develop and validate the prediction model, we divided the data from 2006 as the training cohort data set and the data before 2006 as the validation cohort data set. After the development of the prediction model, we performed a stratified Cox proportional hazards model to compare the RFS between the predicted groups. Results: A total of 585/1351(43.3%) pts were EGFR-m included in the PRISM project. Of all pts, stage I, EGFR-m were 205 pts. The median RFS of the stage I, EGFR-m 123.1 months (m). In the training cohort, the model detected 43 pts for high-risk and 88 pts for low-risk. In the validation cohort, the model predicted 29 pts for high-risk and 45 pts for low-risk. Median RFS of high-risk vs. low-risk were 52.2 m vs. 105 m (HR 2.43, p=0.01). The 1-year RFS rate, 2-year RFS rate, and 5-year RFS rates for high-risk and low-risk pts were 100% vs. 98.5%, 66.7% vs. 89.2%, and 41.7% vs. 66.1%, respectively. Twenty-eight gene set coefficients were non-zero in the prediction model. The gene sets with large positive coefficients that were considered important for prediction as "high risk" were the gene sets affected by KRAS gene overexpression and p53 gene knockdown. In contrast, gene sets repressed by mTOR inhibition and genes repressed by TBK1 gene knockdown and KRAS gene overexpression had large negative coefficients. Conclusions: We developed and validated the prediction model whether the EGFR-m patients will recur within 5 years or not. EGFR-m NSCLC recurrence appears to be high risk with pathways associated with KRAS and p53 genes, and low risk with mutations in the gene sets suppressed by the mTOR pathway and TBK1 gene. [Table: see text]